1.
Dihydroergocryptine
–
Dihydroergocryptine is a dopamine agonist of the ergoline chemical class that is used as an antiparkinson agent. Dihydroergocryptine has been shown to be effective as monotherapy in the early stages of Parkinsons disease. Initial monotherapy with a dopamine agonist is associated with reduced risk for complications in Parkinson patients relative to levodopa. DHEC, like other dopamine agonists, aims to mimic the endogenous neurotransmitter, recent evidence also supports that dopamine receptor agonists, instead of L-DOPA may slow or prevent the progression of Parkinsons disease. Dihydroergocryptine can also be used in migraine prophylaxis, as well as for the treatment of low pressure in elderly patients. More commonly, it is used in combination with two similar compounds, dihydroergocornine and dihydroergocristine and this mixture is called ergoloid or codergocrine. Dihydroergocryptine is a mixture of two similar compounds, alpha- and beta-dihydroergocryptine at a ratio of 2,1. Dihydroergocryptine is an ergot derivative that is also structurally very similar to bromocriptine. DHEC differs in that it is hydrogenated in C9–C10 and lacks bromine in C2, in fact, all ergot derivatives are uniquely or mainly D2-like receptor agonists. Several in vitro and in studies have demonstrated that dihydroergocriptine is an effective anti-Parkinson drug. The Kd of DHEC is found to be around 5-8 nM at D2 receptors, less certain is the contribution of its partial D1 receptor and D3 receptor agonist activity. DHEC has an affinity for D1 and D3 receptors than for D2 receptors. Remarkably, DHEC does not significantly interact with serotonergic and adrenergic receptors, dihydroergocriptine has two main pharmacokinetic advantages over levodopa. The first pharmacokinetic advantage is its half-life of 12 to 16 hours, though the exact reason is not known, continuous stimulation is considered to reduce risk for motor complications. The second pharamcokinetic advantage is the lack of influence on drug absorption. This characteristic also allows for more sustained dopamine receptor stimulation, DHEC can be taken with a single oral dose and is rapidly absorbed. Peak plasma concentrations occur between 30 and 120 minutes after administration, the strong first-pass hepatic metabolism results in poor bioavailability. Less than 5% of the original dosage reaches the circulation, DHEC is also proven to be a safe and effective in improving symptoms in Parkinsons patients

2.
Regulation of therapeutic goods
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The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction. In some countries, such as the United States, they are regulated at the level by a single agency. In other jurisdictions they are regulated at the level, or at both state and national levels by various bodies, as is the case in Australia. The role of therapeutic goods regulation is designed mainly to protect the health, regulation is aimed at ensuring the safety, quality, and efficacy of the therapeutic goods which are covered under the scope of the regulation. In most jurisdictions, therapeutic goods must be registered before they are allowed to be marketed, there is usually some degree of restriction of the availability of certain therapeutic goods depending on their risk to consumers. Therapeutic goods in Australia are regulated by the Therapeutic Goods Administration, there are 5 main categories, Normal Medicines - Cough, cold and fever medicines, antiseptics, vitamins and others. Sold freely in pharmacies and some large supermarkets, red Stripe Medicines - These medicines are sold only with medical prescription. Antibiotics, Anti allergenics, Anti inflammatories, and other medicines, in Brazil, governmental control is loose on this type, it is not uncommon to buy this type of prescription medicine over the counter without a prescription. Red Stripe Psychoactive Medicines - These medicines are only with a Special Control white medical prescription with carbon copy. The original must be retained by the pharmacist after the sale, Drugs include anti-depressants, anti-convulsants, some sleep aids, anti-psychotics and other non-habit-inducing controlled medicines. Though some consider them habit inducing, anabolic steroids are also regulated under this category, black Stripe Medicines - These medicines are sold only with the Blue B Form medical prescription, which is valid for 30 days and must be retained by the pharmacist after the sale. Includes sedatives, some anorexic inducers and other habit-inducing controlled medicines, includes amphetamines and other stimulants, opioids and other strong habit-forming controlled medicines. In Canada, regulation of goods are governed by the Food and Drug Act. In addition, the Controlled Drugs and Substances Act requires additional regulatory requirements for controlled drugs, the regulation of drugs in Burma is governed by the Food and Drug Administration and Food and Drug Board of Authority. The regulation of drugs in China is governed by the China Food, Medicines for Human Use in the United Kingdom are regulated by the Medicines and Healthcare products Regulatory Agency. The availability of drugs is regulated by classification by the MHRA as part of marketing authorisation of a product, Medicines in the Republic of Ireland are regulated according to the Misuse of Drugs Regulations 1988. Controlled drugs are divided into five categories based on their potential for misuse, cD1, cannabis, lysergamide, coca leaf, etc. Use prohibited except in limited circumstances where a license has been granted, CD2, amphetamine, methadone, morphine, fentanyl, oxycodone, tapentadol, etc

3.
PubChem
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PubChem is a database of chemical molecules and their activities against biological assays. The system is maintained by the National Center for Biotechnology Information, a component of the National Library of Medicine, PubChem can be accessed for free through a web user interface. Millions of compound structures and descriptive datasets can be downloaded via FTP. PubChem contains substance descriptions and small molecules with fewer than 1000 atoms and 1000 bonds, more than 80 database vendors contribute to the growing PubChem database. PubChem consists of three dynamically growing primary databases, as of 28 January 2016, Compounds,82.6 million entries, contains pure and characterized chemical compounds. Substances,198 million entries, contains also mixtures, extracts, complexes, bioAssay, bioactivity results from 1.1 million high-throughput screening programs with several million values. PubChem contains its own online molecule editor with SMILES/SMARTS and InChI support that allows the import and export of all common chemical file formats to search for structures and fragments. In the text search form the database fields can be searched by adding the name in square brackets to the search term. A numeric range is represented by two separated by a colon. The search terms and field names are case-insensitive, parentheses and the logical operators AND, OR, and NOT can be used. AND is assumed if no operator is used, example,0,5000,50,10 -5,5 PubChem was released in 2004. The American Chemical Society has raised concerns about the publicly supported PubChem database and they have a strong interest in the issue since the Chemical Abstracts Service generates a large percentage of the societys revenue. To advocate their position against the PubChem database, ACS has actively lobbied the US Congress, soon after PubChems creation, the American Chemical Society lobbied U. S. Congress to restrict the operation of PubChem, which they asserted competes with their Chemical Abstracts Service

4.
ChemSpider
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ChemSpider is a database of chemicals. ChemSpider is owned by the Royal Society of Chemistry, the database contains information on more than 50 million molecules from over 500 data sources including, Each chemical is given a unique identifier, which forms part of a corresponding URL. This is an approach to develop an online chemistry database. The search can be used to widen or restrict already found results, structure searching on mobile devices can be done using free apps for iOS and for the Android. The ChemSpider database has been used in combination with text mining as the basis of document markup. The result is a system between chemistry documents and information look-up via ChemSpider into over 150 data sources. ChemSpider was acquired by the Royal Society of Chemistry in May,2009, prior to the acquisition by RSC, ChemSpider was controlled by a private corporation, ChemZoo Inc. The system was first launched in March 2007 in a release form. ChemSpider has expanded the generic support of a database to include support of the Wikipedia chemical structure collection via their WiChempedia implementation. A number of services are available online. SyntheticPages is an interactive database of synthetic chemistry procedures operated by the Royal Society of Chemistry. Users submit synthetic procedures which they have conducted themselves for publication on the site and these procedures may be original works, but they are more often based on literature reactions. Citations to the published procedure are made where appropriate. They are checked by an editor before posting. The pages do not undergo formal peer-review like a journal article. The comments are moderated by scientific editors. The intention is to collect practical experience of how to conduct useful chemical synthesis in the lab, while experimental methods published in an ordinary academic journal are listed formally and concisely, the procedures in ChemSpider SyntheticPages are given with more practical detail. Comments by submitters are included as well, other publications with comparable amounts of detail include Organic Syntheses and Inorganic Syntheses

5.
ChEMBL
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ChEMBL or ChEMBLdb is a manually curated chemical database of bioactive molecules with drug-like properties. It is maintained by the European Bioinformatics Institute, of the European Molecular Biology Laboratory, based at the Wellcome Trust Genome Campus, Hinxton, the database, originally known as StARlite, was developed by a biotechnology company called Inpharmatica Ltd. later acquired by Galapagos NV. The data was acquired for EMBL in 2008 with an award from The Wellcome Trust, resulting in the creation of the ChEMBL chemogenomics group at EMBL-EBI, the ChEMBL database contains compound bioactivity data against drug targets. Bioactivity is reported in Ki, Kd, IC50, and EC50, data can be filtered and analyzed to develop compound screening libraries for lead identification during drug discovery. ChEMBL version 2 was launched in January 2010, including 2.4 million bioassay measurements covering 622,824 compounds and this was obtained from curating over 34,000 publications across twelve medicinal chemistry journals. ChEMBLs coverage of available bioactivity data has grown to become the most comprehensive ever seen in a public database, in October 2010 ChEMBL version 8 was launched, with over 2.97 million bioassay measurements covering 636,269 compounds. ChEMBL_10 saw the addition of the PubChem confirmatory assays, in order to integrate data that is comparable to the type, ChEMBLdb can be accessed via a web interface or downloaded by File Transfer Protocol. It is formatted in a manner amenable to computerized data mining, ChEMBL is also integrated into other large-scale chemistry resources, including PubChem and the ChemSpider system of the Royal Society of Chemistry. In addition to the database, the ChEMBL group have developed tools and these include Kinase SARfari, an integrated chemogenomics workbench focussed on kinases. The system incorporates and links sequence, structure, compounds and screening data, the primary purpose of ChEMBL-NTD is to provide a freely accessible and permanent archive and distribution centre for deposited data. July 2012 saw the release of a new data service, sponsored by the Medicines for Malaria Venture. The data in this service includes compounds from the Malaria Box screening set, myChEMBL, the ChEMBL virtual machine, was released in October 2013 to allow users to access a complete and free, easy-to-install cheminformatics infrastructure. In December 2013, the operations of the SureChem patent informatics database were transferred to EMBL-EBI, in a portmanteau, SureChem was renamed SureChEMBL. 2014 saw the introduction of the new resource ADME SARfari - a tool for predicting and comparing cross-species ADME targets

6.
European Chemicals Agency
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ECHA is the driving force among regulatory authorities in implementing the EUs chemicals legislation. ECHA helps companies to comply with the legislation, advances the safe use of chemicals, provides information on chemicals and it is located in Helsinki, Finland. The Agency, headed by Executive Director Geert Dancet, started working on 1 June 2007, the REACH Regulation requires companies to provide information on the hazards, risks and safe use of chemical substances that they manufacture or import. Companies register this information with ECHA and it is freely available on their website. So far, thousands of the most hazardous and the most commonly used substances have been registered, the information is technical but gives detail on the impact of each chemical on people and the environment. This also gives European consumers the right to ask whether the goods they buy contain dangerous substances. The Classification, Labelling and Packaging Regulation introduces a globally harmonised system for classifying and labelling chemicals into the EU. This worldwide system makes it easier for workers and consumers to know the effects of chemicals, companies need to notify ECHA of the classification and labelling of their chemicals. So far, ECHA has received over 5 million notifications for more than 100000 substances, the information is freely available on their website. Consumers can check chemicals in the products they use, Biocidal products include, for example, insect repellents and disinfectants used in hospitals. The Biocidal Products Regulation ensures that there is information about these products so that consumers can use them safely. ECHA is responsible for implementing the regulation, the law on Prior Informed Consent sets guidelines for the export and import of hazardous chemicals. Through this mechanism, countries due to hazardous chemicals are informed in advance and have the possibility of rejecting their import. Substances that may have effects on human health and the environment are identified as Substances of Very High Concern 1. These are mainly substances which cause cancer, mutation or are toxic to reproduction as well as substances which persist in the body or the environment, other substances considered as SVHCs include, for example, endocrine disrupting chemicals. Companies manufacturing or importing articles containing these substances in a concentration above 0 and they are required to inform users about the presence of the substance and therefore how to use it safely. Consumers have the right to ask the retailer whether these substances are present in the products they buy, once a substance has been officially identified in the EU as being of very high concern, it will be added to a list. This list is available on ECHA’s website and shows consumers and industry which chemicals are identified as SVHCs, Substances placed on the Candidate List can then move to another list

7.
Chemical formula
–
These are limited to a single typographic line of symbols, which may include subscripts and superscripts. A chemical formula is not a name, and it contains no words. Although a chemical formula may imply certain simple chemical structures, it is not the same as a full chemical structural formula. Chemical formulas can fully specify the structure of only the simplest of molecules and chemical substances, the simplest types of chemical formulas are called empirical formulas, which use letters and numbers indicating the numerical proportions of atoms of each type. Molecular formulas indicate the numbers of each type of atom in a molecule. For example, the formula for glucose is CH2O, while its molecular formula is C6H12O6. This is possible if the relevant bonding is easy to show in one dimension, an example is the condensed molecular/chemical formula for ethanol, which is CH3-CH2-OH or CH3CH2OH. For reasons of structural complexity, there is no condensed chemical formula that specifies glucose, chemical formulas may be used in chemical equations to describe chemical reactions and other chemical transformations, such as the dissolving of ionic compounds into solution. A chemical formula identifies each constituent element by its chemical symbol, in empirical formulas, these proportions begin with a key element and then assign numbers of atoms of the other elements in the compound, as ratios to the key element. For molecular compounds, these numbers can all be expressed as whole numbers. For example, the formula of ethanol may be written C2H6O because the molecules of ethanol all contain two carbon atoms, six hydrogen atoms, and one oxygen atom. Some types of compounds, however, cannot be written with entirely whole-number empirical formulas. An example is boron carbide, whose formula of CBn is a variable non-whole number ratio with n ranging from over 4 to more than 6.5. When the chemical compound of the consists of simple molecules. These types of formulas are known as molecular formulas and condensed formulas. A molecular formula enumerates the number of atoms to reflect those in the molecule, so that the formula for glucose is C6H12O6 rather than the glucose empirical formula. However, except for very simple substances, molecular chemical formulas lack needed structural information, for simple molecules, a condensed formula is a type of chemical formula that may fully imply a correct structural formula. For example, ethanol may be represented by the chemical formula CH3CH2OH

8.
Jmol
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Jmol is computer software for molecular modelling chemical structures in 3-dimensions. Jmol returns a 3D representation of a molecule that may be used as a teaching tool and it is written in the programming language Java, so it can run on the operating systems Windows, macOS, Linux, and Unix, if Java is installed. It is free and open-source software released under a GNU Lesser General Public License version 2.0, a standalone application and a software development kit exist that can be integrated into other Java applications, such as Bioclipse and Taverna. A popular feature is an applet that can be integrated into web pages to display molecules in a variety of ways, for example, molecules can be displayed as ball-and-stick models, space-filling models, ribbon diagrams, etc. Jmol supports a range of chemical file formats, including Protein Data Bank, Crystallographic Information File, MDL Molfile. There is also a JavaScript-only version, JSmol, that can be used on computers with no Java, the Jmol applet, among other abilities, offers an alternative to the Chime plug-in, which is no longer under active development. While Jmol has many features that Chime lacks, it does not claim to reproduce all Chime functions, most notably, Chime requires plug-in installation and Internet Explorer 6.0 or Firefox 2.0 on Microsoft Windows, or Netscape Communicator 4.8 on Mac OS9. Jmol requires Java installation and operates on a variety of platforms. For example, Jmol is fully functional in Mozilla Firefox, Internet Explorer, Opera, Google Chrome, fast and Scriptable Molecular Graphics in Web Browsers without Java3D

9.
Simplified molecular-input line-entry system
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The simplified molecular-input line-entry system is a specification in form of a line notation for describing the structure of chemical species using short ASCII strings. SMILES strings can be imported by most molecule editors for conversion back into two-dimensional drawings or three-dimensional models of the molecules, the original SMILES specification was initiated in the 1980s. It has since modified and extended. In 2007, a standard called OpenSMILES was developed in the open-source chemistry community. Other linear notations include the Wiswesser Line Notation, ROSDAL and SLN, the original SMILES specification was initiated by David Weininger at the USEPA Mid-Continent Ecology Division Laboratory in Duluth in the 1980s. The Environmental Protection Agency funded the project to develop SMILES. It has since modified and extended by others, most notably by Daylight Chemical Information Systems. In 2007, a standard called OpenSMILES was developed by the Blue Obelisk open-source chemistry community. Other linear notations include the Wiswesser Line Notation, ROSDAL and SLN, in July 2006, the IUPAC introduced the InChI as a standard for formula representation. SMILES is generally considered to have the advantage of being slightly more human-readable than InChI, the term SMILES refers to a line notation for encoding molecular structures and specific instances should strictly be called SMILES strings. However, the term SMILES is also used to refer to both a single SMILES string and a number of SMILES strings, the exact meaning is usually apparent from the context. The terms canonical and isomeric can lead to confusion when applied to SMILES. The terms describe different attributes of SMILES strings and are not mutually exclusive, typically, a number of equally valid SMILES strings can be written for a molecule. For example, CCO, OCC and CC all specify the structure of ethanol, algorithms have been developed to generate the same SMILES string for a given molecule, of the many possible strings, these algorithms choose only one of them. This SMILES is unique for each structure, although dependent on the algorithm used to generate it. These algorithms first convert the SMILES to a representation of the molecular structure. A common application of canonical SMILES is indexing and ensuring uniqueness of molecules in a database, there is currently no systematic comparison across commercial software to test if such flaws exist in those packages. SMILES notation allows the specification of configuration at tetrahedral centers, and these are structural features that cannot be specified by connectivity alone and SMILES which encode this information are termed isomeric SMILES

10.
International Chemical Identifier
–
Initially developed by IUPAC and NIST from 2000 to 2005, the format and algorithms are non-proprietary. The continuing development of the standard has supported since 2010 by the not-for-profit InChI Trust. The current version is 1.04 and was released in September 2011, prior to 1.04, the software was freely available under the open source LGPL license, but it now uses a custom license called IUPAC-InChI Trust License. Not all layers have to be provided, for instance, the layer can be omitted if that type of information is not relevant to the particular application. InChIs can thus be seen as akin to a general and extremely formalized version of IUPAC names and they can express more information than the simpler SMILES notation and differ in that every structure has a unique InChI string, which is important in database applications. Information about the 3-dimensional coordinates of atoms is not represented in InChI, the InChI algorithm converts input structural information into a unique InChI identifier in a three-step process, normalization, canonicalization, and serialization. The InChIKey, sometimes referred to as a hashed InChI, is a fixed length condensed digital representation of the InChI that is not human-understandable. The InChIKey specification was released in September 2007 in order to facilitate web searches for chemical compounds and it should be noted that, unlike the InChI, the InChIKey is not unique, though collisions can be calculated to be very rare, they happen. In January 2009 the final 1.02 version of the InChI software was released and this provided a means to generate so called standard InChI, which does not allow for user selectable options in dealing with the stereochemistry and tautomeric layers of the InChI string. The standard InChIKey is then the hashed version of the standard InChI string, the standard InChI will simplify comparison of InChI strings and keys generated by different groups, and subsequently accessed via diverse sources such as databases and web resources. Every InChI starts with the string InChI= followed by the version number and this is followed by the letter S for standard InChIs. The remaining information is structured as a sequence of layers and sub-layers, the layers and sub-layers are separated by the delimiter / and start with a characteristic prefix letter. The six layers with important sublayers are, Main layer Chemical formula and this is the only sublayer that must occur in every InChI. The atoms in the formula are numbered in sequence, this sublayer describes which atoms are connected by bonds to which other ones. Describes how many hydrogen atoms are connected to each of the other atoms, the condensed,27 character standard InChIKey is a hashed version of the full standard InChI, designed to allow for easy web searches of chemical compounds. Most chemical structures on the Web up to 2007 have been represented as GIF files, the full InChI turned out to be too lengthy for easy searching, and therefore the InChIKey was developed. With all databases currently having below 50 million structures, such duplication appears unlikely at present, a recent study more extensively studies the collision rate finding that the experimental collision rate is in agreement with the theoretical expectations. Example, Morphine has the structure shown on the right, as the InChI cannot be reconstructed from the InChIKey, an InChIKey always needs to be linked to the original InChI to get back to the original structure

11.
Ergoline
–
Ergoline is a chemical compound whose structural skeleton is contained in a diverse range of alkaloids. Ergoline derivatives are used clinically for the purpose of vasoconstriction and in the treatment and alleviation of migraines, some ergoline alkaloids found in ergot fungi are implicated in the condition ergotism, which causes convulsive and gangrenous symptoms. Others are psychedelic substances, including LSD and some alkaloids in Argyreia nervosa, Ipomoea tricolor, newer synthetic ergolines used for Parkinsons disease include pergolide and lisuride. Perhaps the most famous derivative is the psychedelic drug LSD. Ergometrine and ergotamine are included as schedule I precursors in the United Nations Convention Against Illicit Traffic in Narcotic Drugs, ergolines can pass into breast milk and should not be used during breastfeeding. They are uterine contractors that can increase the risk of miscarriage during pregnancy, the principal alkaloids in the seeds are ergine and its optical isomer isoergine, with several other lysergic acid derivatives and clavines present in lesser amounts. The Hawaiian species Argyreia nervosa includes similar alkaloids and it is possible, though not proven, that ergine or isoergine are responsible for the psychedelic effects. There may be an origin of the ergoline alkaloids also in the Convolvulaceae. Like the ergot alkaloids in some plants, the ergoline alkaloids found in the plant Ipomoea asarifolia are produced by a seed-transmitted epiphytic clavicipitaceous fungus. Ergoline alkaloids were first isolated from ergot, a fungus that infects grain, ergot also has a long history of medicinal use, which led to attempts to characterize its activity chemically. This began in 1906 with the isolation by G. Barger and F. H. Carr of ergotoxine, with the isolation of ergotamine in 1918 by Arthur Stoll came the first therapeutic use of isolated ergoline alkaloids. With the determination of the chemical structure of the ergot alkaloids in the early 1930s. There are 3 main classes of ergoline derivatives, the amides of lysergic acid, the water-insoluble ergopeptines. This structure comprises proline and two other α-amino acids, linked in an unusual cyclol formation >N-C< with the carbon of proline. Some of the important ergopeptines are summarized below and those deriving from dimethylergoline are referred to as clavines. Examples of clavines, include festuclavine, fumigaclavine A, fumigaclavine C, some synthetic ergoline derivatives do not fall easily into any of the above groups. P. Bock and D. G. Parbery Hofmann, A. Teonanácatl and Ololiuqui, two ancient magic drugs of Mexico Bulletin on Narcotics 197113 TiHKAL #26

12.
Methyl group
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A methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms — CH3. In formulas, the group is often abbreviated Me, such hydrocarbon groups occur in many organic compounds. It is a stable group in most molecules. While the methyl group is part of a larger molecule. The anion has eight electrons, the radical seven and the cation six. All three forms are highly reactive and rarely observed, the methylium cation exists in the gas phase, but is otherwise not encountered. Some compounds are considered to be sources of the CH3+ cation, the methanide anion exists only in rarefied gas phase or under exotic conditions. It can be produced by electrical discharge in ketene at low pressure, such reagents are generally prepared from the methyl halides, M + CH3X → MCH3 where M is an alkali metal. The methyl radical has the formula CH3 and it exists in dilute gases, but in more concentrated form it readily dimerizes to ethane. It can be produced by decomposition of only certain compounds. The reactivity of a methyl group depends on the adjacent substituents, methyl groups can be quite unreactive. For example, in compounds, the methyl group resists attack by even the strongest acids. The oxidation of a group occurs widely in nature and industry. The oxidation products derived from methyl are CH2OH, CHO, for example, permanganate often converts a methyl group to a carboxyl group, e. g. the conversion of toluene to benzoic acid. Ultimately oxidation of methyl groups gives protons and carbon dioxide, as seen in combustion, demethylation is a common process, and reagents that undergo this reaction are called methylating agents. Common methylating agents are dimethyl sulfate, methyl iodide, and methyl triflate, methanogenesis, the source of natural gas, arises via a demethylation reaction. Certain methyl groups can be deprotonated, for example, the acidity of the methyl groups in acetone is about 1020 more acidic than methane. The resulting carbanions are key intermediates in many reactions in organic synthesis and biosynthesis, fatty acids are produced in this way

13.
Biosynthesis
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Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds and this process often consists of metabolic pathways. Some of these pathways are located within a single cellular organelle, while others involve enzymes that are located within multiple cellular organelles. Examples of these pathways include the production of lipid membrane components. The prerequisite elements for biosynthesis include, precursor compounds, chemical energy and these elements create monomers, the building blocks for macromolecules. Biosynthesis occurs due to a series of chemical reactions, for these reactions to take place, the following elements are necessary, Precursor compounds, these compounds are the starting molecules or substrates in a reaction. These may also be viewed as the reactants in a chemical process. Chemical energy, chemical energy can be found in the form of high energy molecules and these molecules are required for energetically unfavorable reactions. Furthermore, the hydrolysis of these compounds drives a reaction forward, high energy molecules, such as ATP, have three phosphates. Often, the phosphate is split off during hydrolysis and transferred to another molecule. Catalytic enzymes, these molecules are special proteins that catalyze a reaction by increasing the rate of the reaction, coenzymes or cofactors, cofactors are molecules that assist in chemical reactions. These may be metal ions, vitamin derivatives such as NADH and acetyl CoA, in the case of NADH, the molecule transfers a hydrogen, whereas acetyl CoA transfers an acetyl group, and ATP transfers a phosphate. Two examples of type of reaction occur during the formation of nucleic acids. For some of these steps, chemical energy is required, Precursor molecule + ATP ↽ − − ⇀ product AMP + PP i Simple compounds that are converted into other compounds with the assistance of cofactors. For example, the synthesis of phospholipids requires acetyl CoA, while the synthesis of another component, shingolipids. The general equation for these examples is, Precursor molecule + Cofactor → e n z y m e macromolecule Simple compounds that join together to create a macromolecule, for example, fatty acids join together to form phopspholipids. In turn, phospholipids and cholesterol interact noncovalently in order to form the lipid bilayer and this reaction may be depicted as follows, Molecule 1 + Molecule 2 ⟶ macromolecule Many intricate macromolecules are synthesized in a pattern of simple, repeated structures. For example, the simplest structures of lipids are fatty acids, fatty acids are hydrocarbon derivatives, they contain a carboxyl group “head” and a hydrocarbon chain “tail. ”These fatty acids create larger components, which in turn incorporate noncovalent interactions to form the lipid bilayer

14.
Proteinogenic amino acid
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Proteinogenic amino acids are amino acids that are incorporated biosynthetically into proteins during translation. The word proteinogenic means protein creating, throughout known life, there are 22 genetically encoded amino acids,20 in the standard genetic code and an additional 2 that can be incorporated by special translation mechanisms. The latter often results from post-translational modification of proteins, some non-proteinogenic amino acids are incorporated into nonribosomal peptides which are synthesized by non-ribosomal peptide synthetases. In some methanogenic prokaryotes, the UAG codon can also be translated to pyrrolysine, in eukaryotes, there are only 21 proteinogenic amino acids, the 20 of the standard genetic code, plus selenocysteine. Humans can synthesize 12 of these from other or from other molecules of intermediary metabolism. The other nine must be consumed, and so they are called essential amino acids, the essential amino acids are histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. The proteinogenic amino acids have been found to be related to the set of amino acids that can be recognized by ribozyme autoaminoacylation systems, thus, non-proteinogenic amino acids would have been excluded by the contingent evolutionary success of nucleotide-based life forms. The following illustrates the structures and abbreviations of the 21 amino acids that are encoded for protein synthesis by the genetic code of eukaryotes. The structures given below are standard chemical structures, not the typical zwitterion forms that exist in aqueous solutions, the masses listed are based on weighted averages of the elemental isotopes at their natural abundances. Forming a peptide bond results in elimination of a molecule of water, general chemical properties §, Values for Asp, Cys, Glu, His, Lys & Tyr were determined using the amino acid residue placed centrally in an alanine pentapeptide. The value for Arg is from Pace et al, the value for Sec is from Byun & Kang. The pKa value of Pyrrolysine has not been reported, note, The pKa value of an amino-acid residue in a small peptide is typically slightly different when it is inside a protein. Protein pKa calculations are used to calculate the change in the pKa value of an amino-acid residue in this situation. In mass spectrometry of peptides and proteins, knowledge of the masses of the residues is useful, the mass of the peptide or protein is the sum of the residue masses plus the mass of water. The residue masses are calculated from the chemical formulas and atomic weights. In mass spectrometry, ions may also one or more protons. § Monoisotopic mass The table below lists the abundance of amino acids in E. coli cells, negative numbers indicate the metabolic processes are energy favorable and do not cost net ATP of the cell. The abundance of amino acids includes amino acids in free form, the proteinogenic set used by known life on Earth appears to be arbitrarily selected by evolution, according to current knowledge, from many hundreds of possible alpha-type amino acids

15.
Isoleucine
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Isoleucine encoded by the codons ATT, ATC, ATA is an α-amino acid that is used in the biosynthesis of proteins. It contains a group, an α-carboxylic acid group. It is essential in humans, meaning the body cannot synthesize it, Isoleucine is synthesized from pyruvate employing leucine biosynthesis enzymes in other organisms such as bacteria. However, in cases, MSUD can lead to damage to the brain cells. As an essential nutrient, it is not synthesized in the body, hence it must be ingested, in plants and microorganisms, it is synthesized via several steps, starting from pyruvic acid and alpha-ketoglutarate. It can also be converted into Acetyl CoA and fed into the TCA cycle by condensing with oxaloacetate to form citrate, in mammals Acetyl CoA cannot be converted back to carbohydrate but can be used in the synthesis of ketone bodies or fatty acids, hence ketogenic. Biotin, sometimes referred to as Vitamin B7 or Vitamin H, is a requirement for the full catabolism of isoleucine. Without adequate biotin, the body will be unable to fully break down isoleucine and leucine molecules. Even though this acid is not produced in animals, it is stored in high quantities. Foods that have high amounts of isoleucine include eggs, soy protein, seaweed, turkey, chicken, lamb, cheese, Isoleucine can be synthesized in a multistep procedure starting from 2-bromobutane and diethylmalonate. Synthetic isoleucine was originally reported in 1905, german chemist Felix Ehrlich discovered isoleucine in hemoglobin in 1903. Center for Biological Sequence Analysis, University of Denmark http, //www. cbs. dtu. dk/courses/27619/codon. html Isoleucine and valine biosynthesis

16.
Leucine
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Leucine is an α-amino acid used in the biosynthesis of proteins. It contains a group, an α-carboxylic acid group. It is essential in humans—meaning the body cannot synthesize it and thus must obtain from the diet, leucine is a major component of the subunits in ferritin, astacin, and other buffer proteins. Leucine is used in the liver, adipose tissue, and muscle tissue, adipose and muscle tissue use leucine in the formation of sterols. Combined leucine use in these two tissues is seven times greater than in the liver, leucine is an essential amino acid in the diet of animals because they lack the complete enzyme pathway to synthesize it de novo from potential precursor compounds. Consequently, they must ingest it, usually as a component of proteins, in healthy individuals, approximately 60% of dietary L-leucine is metabolized after several hours, with roughly 5% of dietary L-leucine being converted to β-hydroxy β-methylbutyric acid. Around 40% of dietary L-leucine is converted to acetyl-CoA, which is used in the synthesis of other compounds. The vast majority of L-leucine metabolism is initially catalyzed by the amino acid aminotransferase enzyme. α-Ketoisocaproate is mostly metabolized by the mitochondrial enzyme branched-chain α-ketoacid dehydrogenase, isovaleryl-CoA is subsequently metabolized by isovaleryl-CoA dehydrogenase and converted to β-methylcrotonoyl-CoA, which is used in the synthesis of acetyl-CoA and other compounds. A relatively small amount of α-KIC is metabolized in the liver by the cytosolic enzyme 4-hydroxyphenylpyruvate dioxygenase, in healthy individuals, this minor pathway – which involves the conversion of L-leucine to α-KIC and then HMB – is the predominant route of HMB synthesis. HMB could be produced via certain metabolites that are generated along this pathway, the metabolism of HMB is initially catalyzed by an uncharacterized enzyme which converts it to HMB-CoA. HMB-CoA is metabolized by either enoyl-CoA hydratase or another uncharacterized enzyme, MC-CoA is then converted by the enzyme methylcrotonyl-CoA carboxylase to methylglutaconyl-CoA, which is subsequently converted to HMG-CoA by methylglutaconyl-CoA hydratase. HMG-CoA is then cleaved into to acetyl-CoA and acetoacetate by HMG-CoA lyase or used in the production of cholesterol via the mevalonate pathway and it is a dietary amino acid with the capacity to directly stimulate muscle protein synthesis. As a dietary supplement, leucine has been found to slow the degradation of tissue by increasing the synthesis of muscle proteins in aged rats. However, results of studies are conflicted. Long-term leucine supplementation does not increase muscle mass or strength in healthy elderly men, more studies are needed, preferably ones based on an objective, random sample of society. Until then, dietary supplemental leucine cannot be associated as the reason for muscular growth or optimal maintenance for the entire population. Leucine potently activates the mammalian target of rapamycin kinase that regulates cell growth, infusion of leucine into the rat brain has been shown to decrease food intake and body weight via activation of the mTOR pathway

17.
International Standard Book Number
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The International Standard Book Number is a unique numeric commercial book identifier. An ISBN is assigned to each edition and variation of a book, for example, an e-book, a paperback and a hardcover edition of the same book would each have a different ISBN. The ISBN is 13 digits long if assigned on or after 1 January 2007, the method of assigning an ISBN is nation-based and varies from country to country, often depending on how large the publishing industry is within a country. The initial ISBN configuration of recognition was generated in 1967 based upon the 9-digit Standard Book Numbering created in 1966, the 10-digit ISBN format was developed by the International Organization for Standardization and was published in 1970 as international standard ISO2108. Occasionally, a book may appear without a printed ISBN if it is printed privately or the author does not follow the usual ISBN procedure, however, this can be rectified later. Another identifier, the International Standard Serial Number, identifies periodical publications such as magazines, the ISBN configuration of recognition was generated in 1967 in the United Kingdom by David Whitaker and in 1968 in the US by Emery Koltay. The 10-digit ISBN format was developed by the International Organization for Standardization and was published in 1970 as international standard ISO2108, the United Kingdom continued to use the 9-digit SBN code until 1974. The ISO on-line facility only refers back to 1978, an SBN may be converted to an ISBN by prefixing the digit 0. For example, the edition of Mr. J. G. Reeder Returns, published by Hodder in 1965, has SBN340013818 -340 indicating the publisher,01381 their serial number. This can be converted to ISBN 0-340-01381-8, the check digit does not need to be re-calculated, since 1 January 2007, ISBNs have contained 13 digits, a format that is compatible with Bookland European Article Number EAN-13s. An ISBN is assigned to each edition and variation of a book, for example, an ebook, a paperback, and a hardcover edition of the same book would each have a different ISBN. The ISBN is 13 digits long if assigned on or after 1 January 2007, a 13-digit ISBN can be separated into its parts, and when this is done it is customary to separate the parts with hyphens or spaces. Separating the parts of a 10-digit ISBN is also done with either hyphens or spaces, figuring out how to correctly separate a given ISBN number is complicated, because most of the parts do not use a fixed number of digits. ISBN issuance is country-specific, in that ISBNs are issued by the ISBN registration agency that is responsible for country or territory regardless of the publication language. Some ISBN registration agencies are based in national libraries or within ministries of culture, in other cases, the ISBN registration service is provided by organisations such as bibliographic data providers that are not government funded. In Canada, ISBNs are issued at no cost with the purpose of encouraging Canadian culture. In the United Kingdom, United States, and some countries, where the service is provided by non-government-funded organisations. Australia, ISBNs are issued by the library services agency Thorpe-Bowker

18.
Dopamine receptor
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Dopamine receptors are a class of G protein-coupled receptors that are prominent in the vertebrate central nervous system. The neurotransmitter dopamine is the endogenous ligand for dopamine receptors. Abnormal dopamine receptor signaling and dopaminergic nerve function is implicated in several neuropsychiatric disorders, thus, dopamine receptors are common neurologic drug targets, antipsychotics are often dopamine receptor antagonists while psychostimulants are typically indirect agonists of dopamine receptors. The existence of multiple types of receptors for dopamine was first proposed in 1976, there are at least five subtypes of dopamine receptors, D1, D2, D3, D4, and D5. The D1 and D5 receptors are members of the D1-like family of receptors, whereas the D2, D3. There is also evidence that suggests the existence of possible D6 and D7 dopamine receptors. At a global level, D1 receptors have widespread expression throughout the brain, furthermore, D1-2 receptor subtypes are found at 10-100 times the levels of the D3-5 subtypes. The D1-like family receptors are coupled to the G protein Gsα, D1 is also coupled to Golf. Gsα subsequently activates adenylyl cyclase, increasing the concentration of the second messenger cyclic adenosine monophosphate. D1 is encoded by the Dopamine receptor D1 gene, D5 is encoded by the Dopamine receptor D5 gene. The D2-like family receptors are coupled to the G protein Giα, D2 is encoded by the Dopamine receptor D2 gene, of which there are two forms, D2Sh and D2Lh, The D2Sh form is pre-synaptically situated, having modulatory functions. The D2Lh form may function as a classical post-synaptic receptor, i. e. transmit information unless blocked by a receptor antagonist or a partial agonist. D3 is encoded by the Dopamine receptor D3 gene, maximum expression of dopamine D3 receptors is noted in the islands of Calleja and nucleus accumbens. D4 is encoded by the Dopamine receptor D4 gene, the D4 receptor gene displays polymorphisms that differ in a variable number tandem repeat present within the coding sequence of exon 3. Some of these alleles are associated with incidence of certain disorders. For example, the D4.7 alleles have an association with attention-deficit hyperactivity disorder. Dopamine receptors have shown to heterodimerize with a number of other G protein-coupled receptors. The D2 class of receptors produce the effect, as they are Gαi coupled receptors

19.
Fenoldopam
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Fenoldopam mesylate is a drug and synthetic benzazepine derivative which acts as a selective D1 receptor partial agonist. Fenoldopam is used as an antihypertensive agent and it was approved by the Food and Drug Administration in September 1997. Fenoldopam is used as an antihypertensive agent postoperatively, and also intravenously to treat a hypertensive crisis, since fenoldopam is the only intravenous agent that improves renal perfusion, in theory it could be beneficial in hypertensive patients with concomitant renal insufficiency. Fenoldopam causes arterial/arteriolar vasodilation leading to a decrease in pressure by activating peripheral D1 receptors. It decreases afterload and also promotes sodium excretion via specific dopamine receptors along the nephron, the renal effect of fenoldopam and dopamine may involve physiological antagonism of the renin-angiotensin system in the kidney. D1 receptor stimulation activates adenylyl cyclase and raises intracellular cyclic AMP, resulting in vasodilation of most arterial beds, including renal, mesenteric, to cause a reduction in systemic vascular resistance. Fenoldopam has an onset of action and short duration of action. Adverse effects include headache, flushing, nausea, hypotension, reflex tachycardia, fenoldopam mesylate contains sodium metabisulfite, a sulfite that may rarely cause allergic-type reactions including anaphylactic symptoms and asthma in susceptible people. Fenoldopam mesylate administration should be undertaken with caution to patients with glaucoma or raised intraocular pressure as fenoldopam raises intraocular pressure

20.
SKF-83,959
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SKF-83,959 is a synthetic benzazepine derivative used in scientific research which acts as an agonist at the D1-D2 dopamine receptor. It behaves as a full agonist at the D1 protomer and a high-affinity partial agonist at the D2 protomer and it was further shown to act as an allosteric modulator of the sigma-1 receptor. SKF-83,959 is a racemate that consists of the R-- and S--enantiomers MCL202 and MCL201, sKF-83,959 inhibits sodium channels as well as delayed rectifier potassium channels. Lee SM, Yang Y, Mailman RB, dopamine D1 receptor signaling, Does GαQ-phospholipase C actually play a role. Lee SM, Kant A, Blake D, et al, sKF-83959 is not a highly-biased functionally selective D1 dopamine receptor ligand with activity at phospholipase C

21.
Cabergoline
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Cabergoline, an ergot derivative, is a potent dopamine receptor agonist on D2 receptors. Rat studies show cabergoline has an inhibitory effect on pituitary lactotroph cells. Also, a study on rats found that cabergoline reduces voluntary alcohol consumption, relatively little is known about the effects of this medication during pregnancy and lactation. In some cases the related bromocriptine may be an alternative when pregnancy is expected, pregnancy, available preliminary data indicates a somewhat increased rate of congenital abnormalities in patients who became pregnant while treated with cabergoline. However, one concluded that foetal exposure to cabergoline through early pregnancy does not induce any increase in the risk of miscarriage or foetal malformation. Lactation, In rats cabergoline was found in the maternal milk, since it is not known if this effect also occurs in humans, breastfeeding is usually not recommended if/when treatment with cabergoline is necessary. Lactation suppression, In some countries cabergoline is sometimes used as a lactation suppressant and it is also used in veterinary medicine to treat false pregnancy in dogs. Cautions, severe cardiovascular disease, Raynauds disease, gastroduodenal ulcers, active gastrointestinal bleeding, Side effects are mostly dose dependent. Much more severe effects are reported for treatment of Parkinsons disease. Cabergoline requires slow dose titration to minimise side effects, the extremely long bioavailability of the medication may complicate dosing regimens during titration and require particular precautions. Approximately 200 patients with newly diagnosed Parkinsons disease participated in a study of cabergoline monotherapy. Seventy-nine percent reported at least one side effect and these side effects were chiefly mild or moderate, GI tract, Side effects were extremely frequent. Fifty-three percent of patients reported side effects, very frequent, Nausea, constipation, and dry mouth. Frequent, Gastric irritation, vomiting, and dyspepsia, psychiatric disturbances and central nervous system, Altogether 51 percent of patients were affected. Very frequent, Sleep disturbances, vertigo, and depression, cardiovascular, Approximately 30 percent of patients experienced side effects. Most frequent were hypotension, peripheral edema and non-specific edema, arrhythmias were encountered in 4. 8%, palpitations in 4. 3%, and angina pectoris in 1. 4%. In a combination study with 2,000 patients also treated with levodopa, encountered side effects required a termination of cabergoline treatment in 15% of patients. Additional side effects were infrequent cases of side effects

22.
Lisuride
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Lisuride is an antiparkinson agent of the iso-ergoline class, chemically related to the dopaminergic ergoline Parkinsons drugs. Lisuride is described as free base and as hydrogen maleate salt, lisuride is used to lower prolactin and, in low doses, to prevent migraine attacks. The use of lisuride as initial anti-Parkinsonian treatment has been advocated, preliminary trials suggest the dermal application of lisuride may be useful in the treatment of Parkinsons disease. Lisuride is not currently available in the US, as the drug was not a success in comparison with other dopamine receptor agonist antiparkinsonian compounds. It is still used clinically in a number of countries in the EU and is commercially available in the UK. Lisuride is a dopamine and a partial agonist for serotonin receptors. It is an antagonist at the serotonin 5-HT2B receptor and it has a high affinity for the dopamine D2, D3 and D4 receptors, as well as serotonin 5-HT1A and 5-HT2A/C receptors. Newer findings suggest the lack of action arises from the phenomenon of biased agonism. Stimulation of the 5-HT2A protomer within the 5-HT2A-mGlu2 receptor complex evokes psychedelic effects, lisuride behaves as an agonist at the 5-HT2AR monomer. Since it competitively antagonises the effects of LSD, it may be regarded as a protomer antagonist of the 5-HT2A-mGluR heteromer, GPCR oligomers are discrete entities and usually possess properties distinct from their parent monomeric receptors

23.
Pergolide
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Pergolide is an ergoline-based dopamine receptor agonist used in some countries for the treatment of Parkinsons disease. Parkinsons disease is associated with low levels of the dopamine in the brain. Pergolide has some of the effects as dopamine in the body. In 2007 pergolide was withdrawn from the U. S. market for use after several published studies revealed a link between the drug and increased rates of valvular heart disease. Pergolide is also used for veterinary purposes, under the trade name Prascend, manufactured by Boehringer Ingelheim, it is commonly used for the treatment of pituitary pars intermedia hyperplasia or Equine Cushings Syndrome in horses. Pergolide acts as an agonist of dopamine D2 and D1 and serotonin 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2B and it may possess agonist activity at other dopamine receptor subtypes as well, similar to cabergoline. The agonist activity of pergolide at the D1 receptor somewhat alters its clinical, the drug is in decreasing use, as it was reported in 2003 to be associated with a form of heart disease called cardiac fibrosis. In 2007, The United States Food and Drug Administration announced a withdrawal of the drug by manufacturers due to the possibility of heart valve damage. Pergolide is not currently available in the United States for human use, pergolide can rarely cause Raynauds phenomenon. Among similar antiparkinsonian drugs, cabergoline but not lisuride exhibit this type of serotonin receptor binding. In January,2007, cabergoline was reported also to be associated with valvular proliferation heart damage, in March 2007, pergolide was withdrawn from the U. S. market for human use, due to serious valvular damage that was shown in two independent studies. Pergolide has also shown to impair associative learning. At least one British pergolide user has attracted media attention with claims that it has caused him to develop a gambling addiction

24.
Terguride
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Terguride, also known as trans-dihydrolisuride, is a serotonin receptor antagonist and dopamine receptor agonist of the ergoline family. It is approved for and used in the treatment of hyperprolactinemia, terguride is an oral, potent antagonist of 5-HT2B and 5-HT2A receptors. Serotonin stimulates the proliferation of pulmonary artery smooth muscle cells, together, this causes vascular remodeling and narrowing of the pulmonary arteries. These changes result in increased resistance and PAH. In May 2008, terguride was granted orphan status for the treatment of pulmonary arterial hypertension. In May 2010 Pfizer purchased worldwide rights for the drug

25.
Dihydrexidine
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Dihydrexidine is a moderately selective full agonist at the dopamine D1 and D5 receptors. It has approximately 10-fold selectivity for D1 and D5 over the D2 receptor, although dihydrexidine has some affinity for the D2 receptor, it has functionally selective D1 signaling, thereby explaining why it lacks D2 agonist behavioral qualities. Dihydrexidine has shown impressive antiparkinson effects in the MPTP-primate model, and has investigated for the treatment of Parkinsons disease. In an early clinical trial the drug was given intravenously and led to profound hypotension so development was halted, the drug was resurrected when it was shown that smaller subcutaneous doses were safe. This led to a study in schizophrenia and current clinical trials to assess its efficacy in improving the cognitive and working memory deficits in schizophrenia. There have been several reviews of relevance to the compound